Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus

Autoria(s): Su, Z.; Gay, L. J.; Strange, A.; Palles, C.; Band, G.; Whiteman, D. C.; Lescai, F.; Langford, C.; Nanji, M.; Edkins, S.; Van Der Winkel, A.; Levine, D.; Sasieni, P.; Bellenguez, C.; Howarth, K.; Freeman, C.; Trudgill, N.; Tucker, A. T.; Pirinen, M.; Peppelenbosch, M. P.; Van Der Laan, L. J. W.; Kuipers, E. J.; Drenth, J. P. H.; Peters, W. H.; Reynolds, J. V.; Kelleher, D. P.; McManus, R.; Grabsch, H.; Prenen, H.; Bisschops, R.; Krishnadath, K.; Siersema, P. D.; Van Baal, J. W. P. M.; Middleton, M.; Petty, R.; Gillies, R.; Burch, N.; Bhandari, P.; Paterson, S.; Edwards, C.; Penman, I.; Vaidya, K.; Ang, Y.; Murray, I.; Patel, P.; Ye, W.; Mullins, P.; Wu, A. H.; Bird, N. C.; Dallal, H.; Shaheen, N. J.; Murray, L. J.; Koss, K.; Bernstein, L.; Romero, Y.; Hardie, L. J.; Zhang, R.; Winter, H.; Corley, D. A.; Panter, S.; Risch, H. A.; Reid, B. J.; Sargeant, I.; Gammon, M. D.; Smart, H.; Dhar, A.; McMurtry, H.; Ali, H.; Liu, G.; Casson, A. G.; Chow, W. H.; Rutter, M.; Tawil, A.; Morris, D.; Nwokolo, C.; Isaacs, P.; Rodgers, C.; Ragunath, K.; MacDonald, C.; Haigh, C.; Monk, D.; Davies, G.; Wajed, S.; Johnston, D.; Gibbons, M.; Cullen, S.; Church, N.; Langley, R.; Griffin, M.; Alderson, D.; Deloukas, P.; Hunt, S. E.; Gray, E.; Dronov, S.; Potter, S. C.; Tashakkori-Ghanbaria, A.; Anderson, M.; Brooks, C.; Blackwell, J. M.; Bramon, E.; Brown, M. A.; Casas, J. P.; Corvin, A.; Duncanson, A.; Markus, H. S.; Mathew, C. G.; Palmer, C. N. A.; Plomin, R.; Rautanen, A.; Sawcer, S. J.; Trembath, R. C.; Viswanathan, A. C.; Wood, N.; Trynka, G.; Wijmenga, C.; Cazier, J. B.; Atherfold, P.; Nicholson, A. M.; Gellatly, N. L.; Glancy, D.; Cooper, S. C.; Cunningham, D.; Lind, T.; Hapeshi, J.; Ferry, D.; Rathbone, B.; Brown, J.; Love, S.; Attwood, S.; MacGregor, S.; Watson, P.; Sanders, S.; Ek, W.; Harrison, R. F.; Moayyedi, P.; De Caestecker, J.; Barr, H.; Stupka, E.; Vaughan, T. L.; Peltonen, L.; Spencer, C. C. A.; Tomlinson, I.; Donnelly, P.; Jankowski, J. A. Z.
Data(s)

2012
Resumo

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.
Identificador

http://eprints.qut.edu.au/89327/
Publicador

Nature Publishing Group
Relação

DOI:10.1038/ng.2408

Su, Z., Gay, L. J., Strange, A., Palles, C., Band, G., Whiteman, D. C., Lescai, F., Langford, C., Nanji, M., Edkins, S., Van Der Winkel, A., Levine, D., Sasieni, P., Bellenguez, C., Howarth, K., Freeman, C., Trudgill, N., Tucker, A. T., Pirinen, M., Peppelenbosch, M. P., Van Der Laan, L. J. W., Kuipers, E. J., Drenth, J. P. H., Peters, W. H., Reynolds, J. V., Kelleher, D. P., McManus, R., Grabsch, H., Prenen, H., Bisschops, R., Krishnadath, K., Siersema, P. D., Van Baal, J. W. P. M., Middleton, M., Petty, R., Gillies, R., Burch, N., Bhandari, P., Paterson, S., Edwards, C., Penman, I., Vaidya, K., Ang, Y., Murray, I., Patel, P., Ye, W., Mullins, P., Wu, A. H., Bird, N. C., Dallal, H., Shaheen, N. J., Murray, L. J., Koss, K., Bernstein, L., Romero, Y., Hardie, L. J., Zhang, R., Winter, H., Corley, D. A., Panter, S., Risch, H. A., Reid, B. J., Sargeant, I., Gammon, M. D., Smart, H., Dhar, A., McMurtry, H., Ali, H., Liu, G., Casson, A. G., Chow, W. H., Rutter, M., Tawil, A., Morris, D., Nwokolo, C., Isaacs, P., Rodgers, C., Ragunath, K., MacDonald, C., Haigh, C., Monk, D., Davies, G., Wajed, S., Johnston, D., Gibbons, M., Cullen, S., Church, N., Langley, R., Griffin, M., Alderson, D., Deloukas, P., Hunt, S. E., Gray, E., Dronov, S., Potter, S. C., Tashakkori-Ghanbaria, A., Anderson, M., Brooks, C., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Duncanson, A., Markus, H. S., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Viswanathan, A. C., Wood, N., Trynka, G., Wijmenga, C., Cazier, J. B., Atherfold, P., Nicholson, A. M., Gellatly, N. L., Glancy, D., Cooper, S. C., Cunningham, D., Lind, T., Hapeshi, J., Ferry, D., Rathbone, B., Brown, J., Love, S., Attwood, S., MacGregor, S., Watson, P., Sanders, S., Ek, W., Harrison, R. F., Moayyedi, P., De Caestecker, J., Barr, H., Stupka, E., Vaughan, T. L., Peltonen, L., Spencer, C. C. A., Tomlinson, I., Donnelly, P., & Jankowski, J. A. Z. (2012) Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus. Nature Genetics, 44(10), pp. 1131-1136.
Direitos

Copyright 2012 Nature America Inc.
Fonte

Faculty of Health; Institute of Health and Biomedical Innovation
Palavras-Chave #allele #article #Barrett esophagus #chromosome 6p #controlled study #female #FOXF1 gene #gene #gene locus #genetic association #genetic predisposition #genetic risk #genetic susceptibility #genetic variability #genotype #human #major clinical study #major histocompatibility complex #male #obesity #organogenesis #priority journal #single nucleotide polymorphism #Adult #Aged #Case-Control Studies #Chromosomes #Human #Pair 16 #Gene Frequency #Genetic Loci #Genetic Predisposition to Disease #Genome-Wide Association Study #Humans #Linkage Disequilibrium #Middle Aged #Models #Genetic #Polymorphism #Single Nucleotide
Tipo

Journal Article
Acesso ao item digital